Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells Journal Article

Authors: Koldehoff, M.; Zakrzewski, J. L.; Klein-Hitpass, L.; Beelen, D. W.; Elmaagacli, A. H.
Article Title: Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells
Abstract: To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, the naturally Gfi-1B overexpressing cell line K562 was cultured in the presence of Gfi-1B target-specific small interfering RNA (siRNA). SiRNA treatment significantly knocked down Gfi-1B expression with an efficiency of nearly 90%. Analysis of the siRNA silencing protocol by colony-forming units ensured that it was not cytotoxic. Samples from Gfi-1B overexpressing cells and cells with knocked-down Gfi-1B were analyzed by oligonucleotide microarray technology and based upon rigorous statistical analysis of the data; relevant genes were chosen for confirmation by reserve transcriptase-polymerase chain reaction, including MYC/MYCBP and CDKN1A. Interestingly, transcripts within components of the signalling cascade of immune cells (PLD1, LAMP1, HSP90, IL6ST), of the tyrosine kinase pathway (TPR, RAC3) and of the transcription factors (RAC3, CEP290, JEM-1, ATR, MYC, SMC3, RARA, RBBP6) were found to be differentially expressed in Gfi-1B overexpressing cells compared to controls. Individual genes such as ZDHHC17, DMXL1, ZNF292 were found to be upregulated in Gfi-1B overexpressing cells. In addition, down-regulated transcripts showed cell signaling transcripts for several chemokine gene members including GNAL, CXCL5, GNL3L, GPR65, TMEM30, BCL11B and transcription factors (GTF2H3, ATXN3). In conclusion, several essential cell signalling factors, as well as transcriptional and post-translational regulation genes were differentially expressed in cells that overexpressed Gfi-1B compared to control cells with knocked-down Gfi-1B. Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations. © 2007 The Japanese Society of Hematology.
Keywords: signal transduction; controlled study; leukemia; unclassified drug; human cell; case-control studies; proto-oncogene proteins; gene overexpression; reverse transcription polymerase chain reaction; gene expression profiling; small interfering rna; transcription factor; cell differentiation; cytotoxicity; tumor cells, cultured; protein tyrosine kinase; oncogene; chemokine; microarray analysis; oligonucleotide array sequence analysis; nucleotide sequence; myc protein; membrane protein; erythroid cell; hematopoietic cell; heat shock protein 90; hematopoiesis; upregulation; gene silencing; cyclin dependent kinase inhibitor 1a; up-regulation; guanine nucleotide binding protein; repressor proteins; leukemia, myelogenous, chronic, bcr-abl positive; atr protein; megakaryocyte; g protein coupled receptor; oncogene myc; rac protein; lysosome associated membrane protein 1; retinoic acid receptor alpha; phospholipase d1; hematopoietic; gfi-1b; k562; ataxin 3; epithelial derived neutrophil activating factor 78; g protein coupled receptor 65; growth factor independent 1b; guanine nucleotide binding protein alpha subunit; guanine nucleotide binding protein alpha subunit 3l; protein bcl11b; protein tmem30; rac 3 protein; transcription factor atr; transcription factor cep290; transcription factor gtf2h3; transcription factor jem1; transcription factor rbbp6
Journal Title: International Journal of Hematology
Volume: 87
Issue: 1
ISSN: 0925-5710
Publisher: Springer Japan KK  
Date Published: 2008-01-01
Start Page: 39
End Page: 47
Language: English
DOI: 10.1007/s12185-007-0013-z
PUBMED: 18224412
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 17 November 2011" - "CODEN: IJHEE" - "Molecular Sequence Numbers: GENBANK: NM_000076, NM_000267, NM_000933, NM_000964, NM_001067, NM_001184, NM_001516, NM_002071, NM_002184, NM_002661, NM_002994, NM_003292, NM_003299, NM_003666, NM_005052, NM_005445, NM_005509, NM_005561, NM_006798, NM_006910, NM_015057, NM_015336, NM_019067, NM_022898, NM_025114, XM_048070, XM_928240;" - "Source: Scopus"
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